The process of surface coating implantable medical articles has proved to be valuable in cases where it is desired to provide the article surface with a property that is not present on the uncoated surface. For example, polymer compositions have been applied to medical devices to improve the wettability and lubricity of surfaces. Coatings can also provide features that improve the biological function of the article. In particular, bioactive agents can be presented on, or delivered from, the article surface to locally or systemically affect blood and vascular components thereby affecting bodily processes such as hemostasis and angiogenesis.
Surface coatings have also been used on implantable medical articles, such as fabrics, to promote a local response leading to thrombus formation. Thrombogenic materials present in surface coatings can provide a sealant function to a medical article, such as cardiac patch, which is typically constructed of porous materials. The sealant coating can promote a thrombogenic response at the coated surface. Factors involved in the thrombogenic response, such as cells involved in tissue repair and matrix factors such as fibrin, associate with the surface of the device and, over time, provide a sealant function to the surface. The thrombogenic response can lead to tissue in-growth in the pores of the device surface and the newly formed tissue can provide a sealant function.
Thrombogenic materials have also been used in connection with vascular occlusion devices such as occlusion coils, wires, or strings. These occlusion devices are typically delivered to a target site within a body lumen, such as an aneurysm, via a catheter. For example, an occlusion coil is advanced into the aneurysm until the coil occupies the aneurysm. These coils are intended to space-fill the aneurysm sac by the volume displaced by the coils themselves, or, if the coil is thrombogenic, in combination with the accumulation of biological material related to the induced thrombus formation in the vicinity of the coils.
Utilizing a thrombogenic coil can provide advantages for the treatment of vascular abnormalities such as aneurysms, but can also be challenging from various standpoints. For example, one challenge is to promote thrombus formation to space-fill the aneurysm without causing embolism, as a result of a portion of the clot dislodging from the aneurysm. In this case, thrombogenic coatings should ideally promote clot formation with reduced risk of embolism. More specifically, thrombogenic coatings should improve the rate and quality of clot maturation and subsequent formation of neointima and neoendothelial coverage near the neck of the aneurysm.
Occlusion coils prepared from uncoated platinum elicit little, if any, of a biological response and therefore are not ideal for promoting rapid thrombus formation in the aneurysm. In order to improve the thrombogenic response, platinum occlusion coils have been coated with collagen. However, the stability of the collagen coating on the coil was poor and the process of delivering the coil to the aneurysm compromised the coating. Therefore, prior art shows that coatings designed to elicit a thrombogenic response suffer from poor quality and therefore insufficient durability.
In addition to difficulties with immobilizing proteins (such as collagen) on these surfaces there are other drawbacks and concerns with using these types of coating materials, particularly animal-derived materials. For example, collagen and gelatin are commonly derived from animal sources and used in many coating applications where a thrombogenic response is desired. One problem associated with use of these materials is that it is difficult to produce consistent coating compositions from these animal sources due to batch-to-batch variations inherent in their production.
In many cases the collagen used in coating technologies is bovine derived. In these cases there is the possibility that bovine collagen preparations may contain unwanted contaminants that are undesirable for introduction into a human subject. One example of an unwanted contaminant is the prionic particles that cause Bovine Spongiform Encephalopathy (BSE).
BSE, also termed Mad Cow Disease, is one of a group of progressive neurological diseases called transmissible spongiform encephalopathies, or TSEs (named for deteriorated areas of the brain that look like sponges). Various forms of TSE have been reported, including scrapie in sheep and chronic wasting disease in elk and mule deer. It is generally believed that the use of recycled animal parts led to the cross-species contamination of scrapie in sheep to mad cow disease, and the ingestion of contaminated beef and bovine products led to the human variant of this disease, Creutzfeldt-Jakob Disease (CJD).
Additional concerns are that preparations from animal sources may provide other unwanted contaminants, such as antigenic factors. These antigenic factors may promote a localized immune response in the vicinity of the implanted article and foul its function. These factors may also cause infection as well as local inflammation.
Overall, the prior art show that coatings on devices that are used in the body to provide hemostatic and occlusion functions, wherein coating designed to elicit a thrombogenic response on the surface of the device, often suffer from poor quality. These coating are not suitable for promoting a local response leading to thrombus formation on the surface of the coated device.